Category: 672948-03-7

Liu, Jian; Kelly, Joseph; Yu, Wensheng; Clausen, Dane; Yu, Younong; Kim, Hyunjin; Duffy, Joseph L.; Chung, Christine C.; Myers, Robert W.; Carroll, Steve; Klein, Daniel J.; Fells, James; Holloway, M. Katharine; Wu, Jin; Wu, Guoxin; Howell, Bonnie J.; Barnard, Richard J. O.; Kozlowski, Joseph A. published the artcile< Selective Class I HDAC Inhibitors Based on Aryl Ketone Zinc Binding Induce HIV-1 Protein for Clearance>, Category: chlorides-buliding-blocks, the main research area is HIV HDAC inhibitor latency LRA zinc binding SAR.

HIV persistence in latently infected, resting CD4+ T cells is broadly considered a barrier to eradicate HIV. Activation of the provirus using latency-reversing agents (LRAs) followed by immune-mediated clearance to purge reservoirs has been touted as a promising therapeutic approach. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) control the acetylation level of lysine residues in histones to regulate the gene transcription. Several clin. HDAC inhibitors had been examined as LRAs, which induced HIV activation in vitro and in vivo. Here we report the discovery of a series of selective and potent class I HDAC inhibitors based on aryl ketones as a zinc binding group, which reversed HIV latency using a Jurkat model of HIV latency in 2C4 cells. The SAR led to the discovery of a highly selective class I HDAC inhibitor 10(I) with excellent potency. HDACi 10 induces the HIV gag P24 protein in patient latent CD4+ T cells.

ACS Medicinal Chemistry Letters published new progress about CD4-positive T cell. 672948-03-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H3NO3, Category: chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Garcia-Barrantes, Pedro M.; Cho, Hyekyung P.; Niswender, Colleen M.; Byers, Frank W.; Locuson, Charles W.; Blobaum, Anna L.; Xiang, Zixiu; Rook, Jerri M.; Conn, P. Jeffrey; Lindsley, Craig W. published the artcile< Development of Novel, CNS Penetrant Positive Allosteric Modulators for the Metabotropic Glutamate Receptor Subtype 1 (mGlu1), Based on an N-(3-Chloro-4-(1,3-dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide Scaffold, That Potentiate Wild Type and Mutant mGlu1 Receptors Found in Schizophrenics>, Synthetic Route of 672948-03-7, the main research area is central nervous system metabotropic glutamate receptor antipsychotic schizophrenic.

The therapeutic potential of selective mGlu1 activation is vastly unexplored relative to the other group I mGlu receptor, mGlu5; therefore, the lab has focused considerable effort toward developing mGlu1 pos. allosteric modulators (PAMs) suitable as in vivo proof of concept tool compounds Optimization of a series of mGlu1 PAMs based on an N-(3-chloro-4-(1,3-dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide scaffold provided I, a potent (mGlu1 EC50 = 31.8 nM) and highly CNS penetrant (brain to plasma ratio (Kp) of 1.02) mGlu1 PAM tool compound, that potentiated not only wild-type human mGlu1 but also mutant mGlu1 receptors derived from deleterious GRM1 mutations found in schizophrenic patients. Moreover, both electrophysiol. and in vivo studies indicate the mGlu1 ago-PAMs/PAMs do not possess the same epileptiform adverse effect liability as mGlu5 ago-PAMs/PAMs and maintain temporal activity suggesting a broader therapeutic window.

Journal of Medicinal Chemistry published new progress about Antipsychotics. 672948-03-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H3NO3, Synthetic Route of 672948-03-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Prabhakar, Virupakshi; Babu, Kondra Sudhakar; Ravindranath, L. K. published the artcile< Design and facile method for synthesis of novel 1,3,4-oxadiazole derivatives by using Biginelli reaction>, Quality Control of 672948-03-7, the main research area is oxadiazole preparation; tetrahydropyrimidine carbohydrazide carboxylic acid Biginelli reaction.

An efficient synthesis of 3,4-dihydropyrimidinones I from the thieno[2,3-d]pyrimidine-6-carboxaldehyde, Et 2-acetoacetate and urea in ethanol, using zirconium tetrachloride as the catalyst is described. A new series of 6-methyl-4-(thieno[2,3-d]pyrimidin-6-yl)-5-(5-p-substituted-1,3,4-oxadiazol-2-yl)-3,4-dihydropyrimidin-2(1H)-one derivatives II (R = C6H5, pyridin-4-yl, furan-2-yl, etc.) was synthesized after refluxing 6-methyl-2-oxo-4-(thieno[2,3-d]pyrimidin-6-yl)-1,2,3,4-tetrahydropyrimidine-5-carbohydrazide with different aromatic/heterocyclic carboxylic acids RC(O)OH in the presence of POCl3.

Heterocyclic Letters published new progress about Aromatic carboxylic acids Role: RCT (Reactant), RACT (Reactant or Reagent). 672948-03-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H3NO3, Quality Control of 672948-03-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Carney, Daniel W.; Lukesh, John C. III; Brody, Daniel M.; Brutsch, Manuela M.; Boger, Dale L. published the artcile< Ultrapotent vinblastines in which added molecular complexity further disrupts the target tubulin dimer-dimer interface>, Application of C4H3NO3, the main research area is ultrapotent vinblastine derivative preparation tubulin binding cancer; chemical synthesis; drug design; protein–protein interaction; tubulin; vinblastine.

Approaches to improving the biol. properties of natural products typically strive to modify their structures to identify the essential pharmacophore, or make functional group changes to improve biol. target affinity or functional activity, change phys. properties, enhance stability, or introduce conformational constraints. Aside from accessible semisynthetic modifications of existing functional groups, rarely does one consider using chem. synthesis to add mol. complexity to the natural product. In part, this may be attributed to the added challenge intrinsic in the synthesis of an even more complex compound Herein, we report synthetically derived, structurally more complex vinblastines inaccessible from the natural product itself that are a stunning 100-fold more active (IC50 values, 50-75 pM vs. 7 nM; HCT116), and that are now accessible because of advances in the total synthesis of the natural product. The newly discovered ultrapotent vinblastines, which may look highly unusual upon first inspection, bind tubulin with much higher affinity and likely further disrupt the tubulin head-to-tail α/β dimer-dimer interaction by virtue of the strategic placement of an added conformationally well-defined, rigid, and extended C20′ urea along the adjacent continuing protein-protein interface. In this case, the added mol. complexity was used to markedly enhance target binding and functional biol. activity (100-fold), and likely represents a general approach to improving the properties of other natural products targeting a protein-protein interaction.

Proceedings of the National Academy of Sciences of the United States of America published new progress about Colorectal carcinoma. 672948-03-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H3NO3, Application of C4H3NO3.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Boogaerts, Ine I. F.; Fortman, George C.; Furst, Marc R. L.; Cazin, Catherine S. J.; Nolan, Steven P. published the artcile< Carboxylation of N-H/C-H Bonds Using N-Heterocyclic Carbene Copper(I) Complexes>, Name: 2-Oxazolecarboxylic acid, the main research area is arene heteroarene regioselective carboxylation copper heterocyclic carbene complex; carboxylic acid aromatic carbamate preparation.

The N-heterocyclic carbene copper(I) complex [Cu(IPr)(OH)] [IPr = 1,3-bis(2,6-diisopropylphenyl)-2-imidazolylidene] was demonstrated to be a synthetically versatile catalyst to enable the regioselective carboxylation of N-H and C-H bonds of arenes and heteroarenes which were predicted to be suitably acidic by Bronsted/Lowry theory.

Angewandte Chemie, International Edition published new progress about Aromatic carboxylic acids Role: SPN (Synthetic Preparation), PREP (Preparation). 672948-03-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H3NO3, Name: 2-Oxazolecarboxylic acid.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Dupuy, Stephanie; Nolan, Steven P. published the artcile< Gold(I)-Catalyzed Protodecarboxylation of (Hetero)Aromatic Carboxylic Acids>, Product Details of C4H3NO3, the main research area is heteroaromatic carboxylic acid decarboxylation gold catalyst protodeauration heterocyclic carbene; N-heterocyclic carbene; catalysis; decarboxylation; gold; protodeauration.

A general protocol for the gold-catalyzed protodecarboxylation of (hetero)aromatic carboxylic acids was developed. It was successfully applied to activated and deactivated benzoic acids and is compatible with a wide range of functionalities. Notably, the reaction requires relatively low catalyst loadings, and the isolation and purification of the reaction products are straightforward. This protocol is both practical and suitable for use in telescoped reaction sequences for which column chromatog. purification is undesirable (e.g., in directed C-H activation/protodecarboxylation/further characterization routes).

Chemistry – A European Journal published new progress about Aromatic carboxylic acids Role: RCT (Reactant), RACT (Reactant or Reagent). 672948-03-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H3NO3, Product Details of C4H3NO3.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Jacobs, Jon; Grum-Tokars, Valerie; Zhou, Ya; Turlington, Mark; Saldanha, S. Adrian; Chase, Peter; Eggler, Aimee; Dawson, Eric S.; Baez-Santos, Yahira M.; Tomar, Sakshi; Mielech, Anna M.; Baker, Susan C.; Lindsley, Craig W.; Hodder, Peter; Mesecar, Andrew; Stauffer, Shaun R. published the artcile< Discovery, Synthesis, And Structure-Based Optimization of a Series of N-(tert-Butyl)-2-(N-arylamido)-2-(pyridin-3-yl) Acetamides (ML188) as Potent Noncovalent Small Molecule Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) 3CL Protease>, Electric Literature of 672948-03-7, the main research area is butylarylamidopyridinyl acetamide preparation; inhibitor severe acute respiratory syndrome coronavirus 3CL protease; SARS CoV inhibitor antiviral preparation.

A high-throughput screen of the NIH mol. libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (I), [(R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844]. Unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, I is a noncovalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multicomponent Ugi reaction was utilized to rapidly explore structure-activity relationships within S1′, S1, and S2 enzyme binding pockets. The X-ray structure of SARS-CoV 3CLpro bound with I was instrumental in guiding subsequent rounds of chem. optimization. I provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.

Journal of Medicinal Chemistry published new progress about Antiviral agents. 672948-03-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H3NO3, Electric Literature of 672948-03-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Yao, Yongqi; Su, Shaoting; Wu, Nan; Wu, Wanqing; Jiang, Huanfeng published the artcile< The cobalt(II)-catalyzed acyloxylation of picolinamides with bifunctional silver carboxylate via C-H bond activation>, Synthetic Route of 672948-03-7, the main research area is picolinamide silver carboxylate cobalt catalyst acyloxylation; acyloxy naphthalenyl picolinamide regioselective preparation.

The cobalt(II)-catalyzed C-H bond acyloxylation of picolinamides with bifunctional silver carboxylate was developed. The operationally simple acyloxylation allowed us to efficiently synthesize 8-functionalized 1-naphthylamine (up to 94% yield) under mild conditions without any addnl. oxidant and base additives. Control experiments were performed to investigate the mechanism of the reaction. This mild and practical acyloxylation approach provide an efficient route for accessing highly functionalized polysubstituted naphthalene compounds and a pathway for modifying drug mols. and natural products.

Organic Chemistry Frontiers published new progress about Acyloxylation (regioselective). 672948-03-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H3NO3, Synthetic Route of 672948-03-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics